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Abstract Hyper progressive disease (HPD) is a paradoxical phenomenon characterized by accelerated tumor growth following treatment with immune checkpoint inhibitors. However, the pathogenic causality and its predictor remain unknown. We herein report a fatal case of HPD in a 50-year-old man with metastatic bladder cancer. He had achieved a complete response (CR) through chemoradiation therapy followed by twelve cycles of chemotherapy, maintaining CR for 24 months. Three weeks after initiating maintenance use of a PD-L1 inhibitor, avelumab, a massive amount of metastases developed, leading to the patient’s demise. Omics analysis, utilizing metastatic tissues obtained from an immediate autopsy, implied the contribution of M2 macrophages, TGF-β signaling, and interleukin-8 to HPD pathogenesis.

Abstract Prognostic stratification is an urgent concern for patients with colorectal cancer (CRC). The desmoplastic reaction (DR) is speculated to mirror the tumor microenvironment. DR types are considered independent prognostic indicators in CRC, but have not been incorporated in previous prognostic nomograms. We aimed to assess the prognostic significance of a novel approach incorporating histopathological indicators reflecting tumor glandular differentiation and microenvironment. We evaluated 329 consecutive patients with CRC who underwent surgical resection at Kansai Medical University. Histological glandular differentiation was scored as 2 (0 point), 3 (1 point), or 4 (2 points). Tumor buddings (TBs) were classified as TB1 (0 point), TB2 (1 point), or TB3 (2 points). pT1 or 2 was considered as 0 point, pT3 or 4 + DR non-immature type as 1 point, and pT3 or 4 + DR immature type as 2 points. Lymph node metastasis was classified as pN0 (0 point), pN1 (1 point), or pN2 (2 points). The preoperative carcinoembryonic antigen levels were categorized as

In the process of investigating synaptic changes happening to mutants lacking postsynaptic receptors in the neuromuscular junction, we focused on a hitherto uncharacterized zebrafish gene zgc153932 whose expression was increased in the RNAseq and droplet digital PCR (ddPCR) analysis of a paralyzed mutant sofa potato. The zgc153932 gene which we named omcin5 (omc5) showed amino acid sequence similarity to human uromodulin and GP2, which are expressed in epithelial cells of the kidney and the gut respectively and bind to bacteria pili. omc5 had 14 paralogues in a ∼400 KB region on the chromosome 12 of the zebrafish genome. These genes, named omcin1 through 15, constitute a gene cluster which presumably arose from recent gene duplications in the zebrafish lineage. An antibody raised against the epitope common to 6–9 genes in the omcin family revealed expression in the cloaca of 1 day post fertilization (dpf) embryos which broadened to the urinary and digestive tracts by 5 dpf. Expression of omc5 was increased by exposure of embryos to Escherichia coli (E. coli). Survival of omc5 mutant embryos was shortened in the presence of E. coli, or when they were not maintained in germ-free conditions. Adults omc5 mutants also exhibited susceptibility to infection. Other teleost species which had omcin-like genes in their genomes showed a range of gene duplication, resulting in clusters of 1 to >15 omcin-like genes. We hereby identified a new gene family specific to teleost that include a microbial induced gene which confers resistance to bacterial infection.

Abstract Background Currently, only limited knowledge is available regarding the phenotypic association between fibroblast growth factor receptor 3 (FGFR3) alterations and the tumor microenvironment (TME) in bladder cancer (BLCA). Methods A multi-omics analysis on 389 BLCA and 35 adjacent normal tissues from a cohort of OMPU-NCC Consortium Japan was retrospectively performed by integrating the whole-exome and RNA-sequence dataset and clinicopathological record. A median follow-up duration of all BLCA cohort was 31 months. Results FGFR3 alterations (aFGFR3), including recurrent mutations and fusions, accounted for 44% of non-muscle invasive bladder cancer (NMIBC) and 15% of muscle-invasive bladder cancer (MIBC). Within MIBC, the consensus subtypes LumP was significantly more prevalent in aFGFR3, whereas the Ba/Sq subtype exhibited similarity between intact FGFR3 (iFGFR3) and aFGFR3 cases. We revealed that basal markers were significantly increased in MIBC/aFGFR3 compared to MIBC/iFGFR3. Transcriptome analysis highlighted TIM3 as the most upregulated immune-related gene in iFGFR3, with differential immune cell compositions observed between iFGFR3 and aFGFR3. Using EcoTyper, TME heterogeneity was discerned even within aFGFR cases, suggesting potential variations in the response to checkpoint inhibitors (CPIs). Among 72 patients treated with CPIs, the objective response rate (ORR) was comparable between iFGFR3 and aFGFR3 (20% vs 31%; p = 0.467). Strikingly, a significantly higher ORR was noted in LumP/aFGFR3 compared to LumP/iFGFR3 (50% vs 5%; p = 0.022). This trend was validated using data from the IMvigor210 trial. Additionally, several immune-related genes, including IDO1, CCL24, IL1RL1, LGALS4, and NCAM (CD56) were upregulated in LumP/iFGFR3 compared to LumP/aFGFR3 cases. Conclusions Differential pathways influenced by aFGFR3 were observed between NMIBC and MIBC, highlighting the upregulation of both luminal and basal markers in MIBC/aFGFR3. Heterogeneous TME was identified within MIBC/aFGFR3, leading to differential outcomes for CPIs. Specifically, a favorable ORR in LumP/aFGFR3 and a poor ORR in LumP/iFGFR3 were observed. We propose TIM3 as a potential target for iFGFR3 (ORR: 20%) and several immune checkpoint genes, including IDO1 and CCL24, for LumP/iFGFR3 (ORR: 5%), indicating promising avenues for precision immunotherapy for BLCA.

Background Aminoglycoside antibiotics are used for treating certain acute infections. However, these drugs cause ototoxicity by inducing inner ear hair cell death. Aims/Objectives We investigated the protective effect of a nanoemulsion of the carotenoid astaxanthin on mammalian inner ear hair cells against neomycin-induced ototoxicity. Material and Methods Dose-response relationship, quantification of hair cell loss, and reactive oxygen species production were assayed in response to neomycin with and without astaxanthin in cultured utricles of CBA/N mice. In addition, auditory brain response (ABR) and hair cell loss after exposure to the nanoformulation and loud noise were examined in vivo in guinea pigs. Results Astaxanthin suppressed neomycin-induced reduction of hair cells by reducing the production of hydroxy radicals. Furthermore, hair cell loss in the second rotation of the cochlea was significantly lower in the astaxanthin group than in the noise-only group. Conclusions and Significance The blood-labyrinth barrier limits the successful delivery of drugs for inner ear complications. However, in the nanoemulsion form, astaxanthin can penetrate the round window (fenestra ovale) membrane, enabling topical administration. Thus, astaxanthin nanoemulsion could be useful in treating ototoxicity in individuals with inner ear complications.

Abstract Background Accessory breast carcinomas of the axilla of males are rare, and primary breast neuroendocrine tumors (BNETs) are rare as well. We present a case of a BNET arising in the axilla of a man. Case presentation A 64-year-old Japanese man presented with a hard 15-mm mass in the axilla and axillary lymph node swelling. Histopathological examination of the incisional biopsy specimen revealed a neuroendocrine carcinoma. Therefore, wide radical excision of the axillary tumor and axillary lymph node dissection were performed. Hematoxylin and eosin staining showed that the solid tumor was mainly located in the subcutaneous adipose tissues and appeared to invade the skin. The tumor phenotypes were positive for CAM 5.2, synaptophysin, estrogen receptor, progesterone receptor, and GATA-binding protein 3; they were negative for human epidermal growth receptor 2. The neuroendocrine component comprised more than 90% of the tumor, and the Ki-67 index was 21%. These results indicated that the tumor was a BNET. This patient underwent adjuvant chemotherapy, endocrine therapy, and radiotherapy. Conclusions BNET cases in males are rare. The clinical and histological criteria as well as treatment for these rare cases are discussed.

Carcinoma in situ (CIS) of the urinary tract comprises 1–3% of all urothelial malignancies and is often a precursor to muscle-invasive urothelial carcinoma (UC). This study aimed to examine the expression profiles of preferentially expressed antigen in melanoma (PRAME), a cancer/testis antigen, and assess its diagnostic and therapeutic applications in CIS, given that its expression in UC has been minimally studied and has not yet been analyzed in CIS. We selected consecutive patients with CIS who underwent biopsy and/or transurethral tumor resection at the Osaka Medical and Pharmaceutical University Hospital. Immunohistochemical staining for PRAME and p53 was performed. Overall, 53 patients with CIS (6 females and 47 males) were included. Notably, PRAME expression was observed in 23 of the 53 patients (43.4%), whereas it was absent in the non-neoplastic urothelial epithelium. Furthermore, no correlation was found between PRAME expression and aberrant p53 expression. Therefore, PRAME expression may serve as a useful marker for CIS of the urinary tract. Furthermore, PRAME may be a candidate for the novel therapeutic target for standard treatment-refractory CIS patients.

Abstract Objective Mucoepidermoid carcinoma (MEC) is the most common malignancy of the parotid gland, but the outcome depends on the histological grade. Therefore, the aim of this study was to evaluate MEC on the basis of histological grade. Study Design Retrospective analysis. Methods We performed a retrospective analysis of data from patients whose initial treatment for MEC of the parotid gland was performed at our department between 1999 and 2021. We examined the association between the Armed Forces Institute of Pathology (AFIP) grade and outcome. Results The AFIP grades were as follows: low, 26 cases; intermediate, 9 cases; and high, 31 cases. About 50% of cases were correctly diagnosed as malignant, and both grade and histology were accurately determined by fine‐needle aspiration cytology in 20% of cases. The 5‐year disease‐free survival rate was 95.5% and 53.8% in the low‐/intermediate‐ and high‐grade cases, respectively. In the high‐grade group, cases with recurrence were found to have a higher rate of lymph nodes metastasis than cases without recurrence. Furthermore, in this high‐grade group, total sacrifice of the facial nerve did not reduce local recurrence. However, radical resection in the cases without tumor invasion to the nerve has decreased the local recurrence rate. The CRTC1‐MAML2 fusion gene was expressed in 42.3% of low‐/intermediate‐ and 14.3% of high‐grade cases. Conclusions The survival rate in MEC was quite different between the low‐/intermediate‐ and high‐grade cases. However, the rate of correct assessment of the grade by fine‐needle aspiration cytology was poor. In high‐grade cases, total sacrifice of the facial nerve may improve the rate of local recurrence in cases without invasion of the main trunk of the nerve. Expression of the CRTC1‐MAML2 fusion gene could be helpful in not only the assessment of grade but the prediction of recurrence. Level of Evidence 4

Purpose: We present a case of a gastrointestinal stromal tumor (GIST) metastasis of the rectal primary resisting chemotherapy to the right orbit 15 years after excision of the primary lesion. Observations: A 79-year-old man was diagnosed with rectal GIST at the age of 65 years and underwent rectal amputation. He underwent hepatectomy for GIST liver metastases at the age of 69 years and pericardiectomy for GIST pericardial metastases at 72 years of age. At the age of 79 years, positron emission tomography-computed tomography revealed the possibility of liver metastasis and metastasis to the right orbit of 10 mm in size. Magnetic resonance imaging revealed a well-circumscribed mass of 10 mm × 12 mm in the deep medial rectus muscle of the right orbit, which was referred to our department for ophthalmic examination. The latter revealed only mild abduction disorder in the right eye. Although chemotherapy was initiated, the tumor gradually increased, causing exophthalmos in the right eye, visual field impairment due to optic nerve exclusion, and decreased visual acuity. Due to repeated multiple metastases, the patient underwent right orbital exenteration and free flap reconstruction at the age of 83 years for radical cure. Pathological examination revealed c-Kit positive, CD34 positive, S100 protein minority positive, MIB-1 positive rate of 10% or more, and α-SMA negative, and the diagnosis was intraorbital metastasis of GIST. Conclusions and importance: Orbital metastases in GISTs are extremely rare, and there is no established standard treatment. Therefore, a comprehensive decision must be made based on the final treatment goal and the patient's background when selecting treatment.

Abstract Background The prevalence of programmed death-ligand 1 (PD-L1) and PD-L2 expression on tumor cells and tumor-infiltrating immune cells in primary central nervous system lymphoma (PCNSL) remains unclear. In the present study, we analyzed needle biopsy and craniotomy specimens of patients with PCNSL to compare the PD-L1 and PD-L2 levels in the tumor and surrounding (peritumoral) tissue. We also assessed the correlation between biological factors and the prognostic significance of PD-L1 and PD-L2 expression. Methods We retrospectively analyzed the cases of 70 patients histologically diagnosed with PCNSL (diffuse large B-cell lymphoma). Immunohistochemistry for CD20, CD68, PD-L1, and PD-L2 was performed. In cases with specimens taken by craniotomy, the percentages of PD-L1- and PD-L2-positive macrophages were evaluated in both tumor and peritumoral tissue. The Kaplan-Meier method with log-rank test and Cox proportional hazard model were used for survival analysis. Results The tumor cells expressed little or no PD-L1 and PD-L2, but macrophages expressed PD-L1 and PD-L2 in most of the patients. The median percentage of PD-L2-positive cells was significantly higher among peritumoral macrophages (32.5%; 95% CI: 0–94.6) than intratumoral macrophages (27.5%; 95% CI: 0–81.1, p = 0.0014). There was a significant correlation between the percentages of PD-L2-positive intratumoral macrophages and PD-L2-positive peritumoral macrophages (p = 0.0429), with very low coefficient correlation (ρ = 0.098535). PD-L1 expression on macrophages was significantly associated with biological factors (intratumoral macrophages: better KPS, p = 0.0008; better MSKCC score, p = 0.0103; peritumoral macrophages: low proportion of LDH elevation, p = 0.0064) and longer OS (for intratumoral macrophages: high PD-L1 = 60 months, 95% CI = 30–132.6; low PD-L1 = 24 months, 95% CI = 11–48; p = 0.032; for peritumoral macrophages: high PD-L1 = 60 months, 95% CI = 30.7–NR; low PD-L1 = 14 months, 95% CI = 3–26). PD-L1 expression on peritumoral macrophages was strongly predictive of a favorable outcome (HR = 0.30, 95% CI = 0.12–0.77, p = 0.0129). Conclusions Macrophages in intratumoral and peritumoral tissue expressed PD-L1 and PD-L2 at a higher rate than tumor cells. PD-L1 expression, especially on peritumoral macrophages, seems to be an important prognostic factor in PCNSL. Future comprehensive analysis of checkpoint molecules in the tumor microenvironment, including the peritumoral tissue, is warranted.

Abstract Background Ovarian granulosa cell tumors (GCTs) are divided into adult GCT (AGCT) and juvenile GCT (JGCT). The AGCT is more common type, conversely, less than 5% of tumors are the JGCT and occur in mainly premenarchal girls and in women younger than 30 years. Although JGCT have different histologic features compared to AGCT, the two types have similar imaging features because they have similar gross appearance. Therefore, it is difficult to distinguish two types by radiologic findings. In addition, it has not been described about the growth rate of JGCTs in past literatures. The aims of this report were to describe a case of rapidly growing JGCT arising in adult with difficulty in diagnosing and to review the literatures. Case presentation A 38-year-old woman, presented with abdominal distension and frequent urination, was found to have a pelvic mass measuring approximately 12 cm on ultrasonography. On magnetic resonance imaging (MRI), right ovarian multiloculated cystic mass accompanied with hemorrhagic foci was demonstrated. Although the presumptive diagnosis of GCT was made based on MR findings, the intraoperative differential diagnoses included GCT, yolk sac tumor or malignant mucinous tumor due to cytologic atypia and lack of the typical findings for AGCT such as nuclear grooves and Call-Exner bodies. As a result, abdominal simple total hysterectomy, bilateral oophoro-salpingectomy, partial omentectomy and appendectomy were performed. Moreover, she had a history of laparoscopic uterine myomectomy about one year before, and during that surgery bilateral ovaries were found to be macrospically normal. Therefore, it was suspected the tumor became enlarged within the short period of time. Conclusions Even though it is difficult to distinguish two types of GCT by imaging findings, in some cases without typical findings for AGCT pathologically, MRI could provide useful information in accurately diagnosing JGCT. Moreover, in this case, the tumor growth rate seemed to be rapid regardless of its borderline malignant potential. It may be related with nuclear atypia and high mitotic rate of the tumor.

BackgroundParotid cancer is relatively rare, and malignancy varies; therefore, novel markers are needed to predict prognosis. Recent advances in matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS), useful for visualization of lipid molecules, have revealed the relationship between cancer and lipid metabolism, indicating the potential of lipids as biomarkers. However, the distribution and importance of phospholipids in parotid cancer remain unclear.ObjectiveThis study aimed to use MALDI-IMS to comprehensively investigate the spatial distribution of phospholipids characteristically expressed in human parotid cancer tissues.MethodsTissue samples were surgically collected from two patients with parotid cancer (acinic cell carcinoma and mucoepidermoid carcinoma). Frozen sections of the samples were assessed using MALDI-IMS in both positive and negative ion modes, with an m/z range of 600-1000. The mass spectra obtained in the tumor and non-tumor regions were compared and analyzed. Ion images corresponding to the peak characteristics of the tumor regions were visualized.ResultsSeveral candidate phospholipids with significantly different expression levels were detected between the tumor and non-tumor regions. The number of unique lipid peaks with significantly different intensities between the tumor and non-tumor regions was 95 and 85 for Cases 1 and 2, respectively, in positive ion mode, and 99 and 97 for Cases 1 and 2, respectively, in negative ion mode. Imaging differentiated the characteristics that phospholipids were heterogeneously distributed in the tumor regions.ConclusionPhospholipid candidates that are characteristically expressed in human parotid cancer tissues were found, demonstrating the localization of their expression. These findings are notable for further investigation of alterations in lipid metabolism of parotid cancer and may have potential for the development of phospholipids as biomarkers.

Abstract Background Serous borderline tumor (SBT) of the micropapillary type (SBT-MP) became one of the major pathological SBT diagnoses in addition to typical SBT, and was also defined as “non-invasive” low-gradeserous carcinoma according to the World Health Organization (WHO) classification in 2014. In this study, we investigated the MRI appearance of SBT-MP compared to that of typical SBT in order to identify specific imaging features of SBT-MP that correspond to pathological findings. Methods MR images of 6 histologically proven ovarian SBT-MP in four patients and 14 typical SBT in ten patients were reviewed retrospectively. Images were evaluated for laterality, size and morphology of the lesion and the solid component (SC) and signal intensity (SI) of the SC. MRI findings were correlated with pathological findings. Results The patients with SBT-MP (mean 26.3 years) were younger than those with typical SBT (mean 44.5 years). Postoperative staging in patients with SBT-MP was II in two and III in two cases, while staging for typical SBT was I in seven, II in one and III in two cases. The morphologic patterns of SBT-MP were a unilateral cystic mass with intracystic mural nodules (CwMN) (n = 2), bilateral solid papillary masses (SM), and bilateral SM with CwMN. The pattern of typical SBT was CwMN (n = 13) in all but one lesion (SM with CwMN). All SCs showed inhomogeneous slight hyperintensity on T2 weighted images (WI) and high SI on diffusion-WI (DWI) except for in one typical SBT. Although diffuse proliferation of the tumor cells in micropapillary projections with little stroma seemed to correspond to inhomogeneous slightly hyperintense foci in SC on T2WI and high SI on DWI, similar MR findings were observed in typical SBT in all lesions on T2WI and 11 of 12 lesions on DWI. In typical SBT, inhomogeneous slightly hyperintense foci in SC on T2WI and high SI on DWI corresponded to highly cellular foci with densely branched papillae. Conclusion Pathological findings and clinical behavior of SBT-MP differed from those of typical SBT, but morphology and SI of SC on MRI were similar, with papillary projections demonstrating inhomogeneous slight hyperintensity on T2WI and high SI on DWI.

Abstract Background Intestinal endometriosis is a common benign disease among menstruating women that affects the intestinal tract. Case presentation This case report presents seven Japanese cases of intestinal endometriosis with colorectal cancer treated by laparoscopic surgery. Five of the seven cases reported here are women presenting with bowel obstruction due to colorectal endometriosis with colorectal cancer. It can be confused with serious lesions such as advanced colorectal cancer with peritoneal involvement or invasion of adjacent organs (T4). Conclusions Therefore, we should consider the probability that the cause of bowel obstruction is not T4 but intestinal endometriosis. For surgical treatment, we recommend laparoscopic surgery for colorectal resection because of its benefits of differential diagnosis of T4, preserving fertility, and preventing excessive surgical stress. We performed laparoscopic resection in seven patients with intestinal endometriosis and colorectal cancer. These cases demonstrate the difficulty of establishing a differential diagnosis of intestinal endometriosis with colorectal cancer from T4.

Activation of peroxisome proliferator-activated receptor (PPAR) α disrupts growth-related activities in a variety of human cancers. This study was designed to determine whether fenofibrate, a PPARα agonist, can suppress 4-nitroquinoline 1-oxide (4-NQO)-induced proliferative lesions in the lung of obese hyperlipidemic mice. Male Tsumura Suzuki Obese Diabetic mice were subcutaneously injected with 4-NQO to induce lung proliferative lesions, including adenocarcinomas. They were then fed a diet containing 0.01% or 0.05% fenofibrate for 29 weeks, starting 1 week after 4-NQO administration. At week 30, the incidence and multiplicity (number of lesions/mouse) of pulmonary proliferative lesions were lower in mice treated with 4-NQO and both doses of fenofibrate compared with those in mice treated with 4-NQO alone. The incidence and multiplicity of lesions were significantly lower in mice treated with 4-NQO and 0.05% fenofibrate compared with those in mice treated with 4-NQO alone (p < 0.05). Both doses of fenofibrate significantly reduced the proliferative activity of the lesions in 4-NQO-treated mice (p < 0.05). Fenofibrate also significantly reduced the serum insulin and insulin-like growth factor (IGF)-1 levels, and decreased the immunohistochemical expression of IGF-1 receptor (IGF-1R), phosphorylated Akt, and phosphorylated Erk1/2 in lung adenocarcinomas. Our results indicate that fenofibrate can prevent the development of 4-NQO-induced proliferative lesions in the lung by modulating the insulin-IGF axis.

We report an extremely rare case with bilateral and symmetric dumbbell ganglioneuromas of the cervical spine in an elderly patient. A 72-year-old man came by ambulance to our hospital due to progressive incomplete paraplegia. Magnetic resonance imaging demonstrated bilateral symmetric dumbbell tumors at the C1/2 level. We performed total resection of the intracanalar tumor, aiming at complete decompression of the spinal cord, and partial and subtotal resection of foraminal outside portions. Histopathological examination of the surgical specimen indicated the tumor cells to be spindle cells with the presence of ganglion cells and no cellular pleomorphism, suggesting a diagnosis of ganglioneuroma. Although the surgery was not curative, the postoperative course was uneventful and provided a satisfactory outcome. This is the fourth known case of cervical ganglioneuromas of the bilateral symmetric dumbbell type.

The numbers of obese people and diabetic patients are ever increasing. Obesity and diabetes are high-risk conditions for chronic diseases, including certain types of cancer, such as colorectal cancer (CRC). The aim of this study was to develop a novel animal model in order to clarify the pathobiology of CRC development in obese and diabetic patients. We developed an animal model of obesity and colorectal cancer by breeding the C57BL/KsJ-db/db (db/db) mouse, an animal model of obesity and type II diabetes, and the C57BL/6J-ApcMin/+ (Min/+) mouse, a model of familial adenomatous polyposis. At 15 weeks of age, the N9 backcross generation of C57BL/KsJ-db/db-ApcMin/+ (db/db-Min/+) mice developed an increased incidence and multiplicity of adenomas in the intestinal tract when compared to the db/m-Min/+ and m/m-Min/+ mice. Blood biochemical profile showed significant increases in insulin (8.3-fold to 11.7-fold), cholesterol (1.2-fold to 1.7-fold), and triglyceride (1.2-fold to 1.3-fold) in the db/db-Min/+ mice, when compared to those of the db/m-Min/+ and m/m-Min/+ mice. Increases (1.4-fold to 2.6-fold) in RNA levels of insulin-like growth factor (IGF)-1, IRF-1R, and IGF-2 were also observed in the db/db-Min/+ mice. These results suggested that the IGFs, as well as hyperlipidemia and hyperinsulinemia, promoted adenoma formation in the db/db-Min/+ mice. Our results thus suggested that the db/db-Min/+ mice should be invaluable for studies on the pathogenesis of CRC in obese and diabetes patients and the therapy and prevention of CRC in these patients.

We present the computed tomography (CT) and magnetic resonance (MR) imaging findings of a 71-year-old woman with a cardiac extension of intravenous leiomyoma (IVL) that arose from the uterus, extended to the inferior vena cava (IVC), and reached the right ventricle through the right ovarian vein. Radiologic-pathologic correlation showed that the intravascular cord-like mass originating from the IVC and extending to the right ventricle was composed of degenerated smooth muscle cells with a number of large vessels that were regarded as arteries; moreover, the arteries within the cord-like mass appeared to be looping internally. Given the disappearance of the right ovarian venous wall around the IVL pathologically, extracting the tumor from the ovarian vein during an operation is considered to be impossible retrospectively. Also it was difficult to identify even the intravenous extension of the uterine leiomyoma histopathologically. Therefore, contrast-enhanced CT, in particular arterial phase imaging, provided important information that revealed the mass, range, and path of the lesion, ensuring that an appropriate operative plan could be drawn up and the tumor completely excised.

It is well known that the production of free radicals is associated with sensory cell death induced by an aminoglycoside. Many researchers have reported that antioxidant reagents protect sensory cells in the inner ear, and coenzyme Q10 (CoQ10) is an antioxidant that is consumed as a health food in many countries. The purpose of this study was to investigate the role of CoQ10 in mammalian vestibular hair cell death induced by aminoglycoside. Cultured utricles of CBA/CaN mice were divided into three groups (control group, neomycin group, and neomycin + CoQ10 group). In the neomycin group, utricles were cultured with neomycin (1 mM) to induce hair cell death. In the neomycin + CoQ10 group, utricles were cultured with neomycin and water-soluble CoQ10 (30-0.3 µM). Twenty-four hours after exposure to neomycin, the cultured tissues were fixed, and vestibular hair cells were labeled using an anti-calmodulin antibody. Significantly more hair cells survived in the neomycin + CoQ10 group than in the neomycin group. These data indicate that CoQ10 protects sensory hair cells against neomycin-induced death in the mammalian vestibular epithelium; therefore, CoQ10 may be useful as a protective drug in the inner ear.